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Современные представления о роли инсулиноподобных и вазоэндотелиальных факторов роста в развитии, прогнозе и таргетной терапии рака яичников
Князев Р.И., Поддубная И.В., Баринов В.В., Бокин И.И. Современные представления о роли инсулиноподобных и вазоэндотелиальных факторов роста в развитии, прогнозе и таргетной терапии рака яичников. Современная онкология. 2015; 17 (3): 105–108.
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Knyazev R.I., Poddubnaya I.V., Barinov V.V., Bokin I.I. Current understanding of the role of insulin-like and vascular endothelial growth factors in development, prognosis and targeted therapy in patients with ovarian cancer. Journal of Modern Oncology. 2015; 17 (3): 105–108.
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Аннотация
Система инсулиноподобных факторов роста (ИФР) посредством своих митогенных и антиапоптотических эффектов играет немаловажную роль в канцерогенезе. При взаимодействии со своим рецептором ИФР активирует Ras- и Akt-сигнальные пути, что приводит к усилению клеточной пролиферации и угнетению апоптоза. Через стимуляцию проангиогенных факторов, в том числе и фактора роста эндотелия сосудов (VEGF – vascular endothelial growth factor), ИФР-сигнальный путь также опосредует процессы неоангиогенеза, необходимые для развития, прогрессирования и метастазирования злокачественных новообразований. Работы последних лет установили связь между ИФР, VEGF и раком яичников. Новые лекарственные препараты таргетной терапии больных карциномой яичника, направленные на подавление компонентов системы ИФР и VEGF, находятся на стадии экспериментальных и клинических исследований. В обзоре литературы представлены результаты изучения роли ИФР и VEGF в развитии, прогнозе и лечении пациенток, страдающих злокачественными новообразованиями яичников.
Ключевые слова: рак яичников, инсулиноподобные факторы роста, фактор роста эндотелия сосудов, прогноз, таргетная терапия.
Ключевые слова: рак яичников, инсулиноподобные факторы роста, фактор роста эндотелия сосудов, прогноз, таргетная терапия.
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The system of the insulin-like growth factors (IGF) through its mitogenic and antiapoptotic effects plays an important role in carcinogenesis. IGF with interaction with own receptor activates Ras- and Akt-signaling pathways that lead to enhanced cell proliferation and reduction of apoptosis. Via stimulation of proangiogenic factors, such as vascular endothelial growth factor (VEGF), IGF also mediates processes of neoangiogenesis that are necessary for the development, progression and metastasis of malignant tumors. Recent data show a linkage between IGF, VEGF and ovarian cancer. New drugs of targeted therapy for patients with ovarian adenocarcinoma, that inhibit the components of IGF and VEGF families, are under experimental and clinical trials. This review presents the results of investigations of IGF′ and VEGF′ role in the development, prognosis and treatment of patients with ovarian cancer.
Key words: ovarian cancer, insulin-like growth factor, vascular endothelial growth factor, prognosis, targeted therapy.
Полный текст
Список литературы
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7. Bao B et al. Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment. PloS one 2012; 7 (12): e50165.
8. Baxter RC. IGF binding proteins in cancer: mechanistic and clinical insights. Nature Rev Cancer 2014; 14 (5): 329–41.
9. Belfiore A, Malaguarnera R. Insulin receptor and cancer. Endocrine-related cancer 2011; 18 (4): R125–R147.
10. Beltran PJ et al. Ganitumab (AMG 479) Inhibits IGF-II–Dependent Ovarian Cancer Growth and Potentiates Platinum-Based Chemotherapy. Clin Cancer Res 2014; 20 (11): 2947–58.
11. Brokaw J et al. IGF-I in epithelial ovarian cancer and its role in disease progression. Growth Factors 2007; 25 (5): 346–54.
12. Bruchim I et al. BRCA1/2 germline mutations in Jewish patients with uterine serous carcinoma. Int J Gynecol Cancer 2010; 20; 7: 1148–53.
13. Bruchim I, Sarfstein R, Werner H. The IGF hormonal network in endometrial cancer: functions, regulation, and targeting approaches. Frontiers in Endocrinol 2014; 5.
14. Brustmann H. Vascular endothelial growth factor expression in serous ovarian carcinoma: relationship with topoisomerase IIa and prognosis. Gynecol Oncol 2004; 95 (1): 16–22.
15. Burger RA et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011; 365 (26): 2473–83.
16. Cao Y et al. Prediagnostic plasma IGFBP‐1, IGF‐1 and risk of prostate cancer. Int J Cancer 2015; 136 (10): 2418–26.
17. Chakraborty AK, Welsh A, DiGiovanna MP. Co-targeting the insulin-like growth factor I receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer cell lines. Breast Cancer Res Treat 2010; 120 (20): 327–35.
18. Chen H et al. Correlation of the expressions of VEGF-C and VEGFR-3 to the pathological grade of prostate cancer. Nan fang yi ke da xue xue bao. J South Med Univ 2011; 31 (1): 155–9.
19. Cheng D, Liang B, Li Y. Serum vascular endothelial growth factor (VEGF-C) as a diagnostic and prognostic marker in patients with ovarian cancer. PloS One 2013; 8 (2): e55309.
20. Crociani O et al. hERG1 channels regulate VEGF-A secretion in human gastric cancer: clinicopathological correlations and therapeutical implications. Clin Cancer Res 2014; 20 (6): 1502–12.
21. Evans T et al. Phase I dose-escalation study of continuous oral dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR), in patients with advanced solid tumors. ASCO Meeting Abstracts 2010; 28: 2531.
22. Flannery CA et al. SAT-0017: Differential Expression of IR-a, IR-B and IGF-1R in Endometrium Reflects Physiology during the Menstrual Cycle and Demonstrates a Distinct Expression Signature in Endometrial Adenocarcinoma. 2014.
23. Gadducci A et al. Vascular endothelial growth factor (VEGF) expression in primary tumors and peritoneal metastases from patients with advanced ovarian carcinoma. Anticancer Res 2002; 23 (3C): 3001–8.
24. Gao J et al. Targeting the insulin-like growth factor axis for the development of novel therapeutics in oncology. Cancer Res 2012; 72 (10): 3–12.
25. Garcı́a-Echeverrı́a C et al. In vivo antitumor activity of NVP-AEW541—a novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell 2004; 5 (3): 231–9.
26. Gotlieb WH et al. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol 2012; 13 (20): 154–62.
27. Guleria S, Sharma J, Kaushik S. Laron syndrome. J Postgraduate Med 2014; 60 (3): 322.
28. Gungor A et al. FRI-319: Hypoinsulinemic Hypoglycemia Secondary to Solitary Fibrous Tumor of the Pleura: Doege-Potter Syndrome; A Case Report 2015.
29. Haluska P et al. Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Clin Cancer Res 2014; 20 (18): 4747–57.
30. Harb WA et al. Final results of a phase I study evaluating the combination of linsitinib, a dual inhibitor of insulin-like growth factor-1 receptor (IGF-1R), and insulin receptor (IR) with weekly paclitaxel (PAC) in patients (Pts) with advanced solid tumors. J Clin Oncol 2013; 31 (15).
31. He L, He J, Zhao X. Expression of VEGF‐D in epithelial ovarian cancer and its relationship to lymphatic metastasis. Asia‐Pacific J Clin Oncol 2013.
32. Herr D et al. VEGF induces ascites in ovarian cancer patients via increasing peritoneal permeability by downregulation of Claudin 5. Gynecol Oncol 2012; 127 (1): 210–6.
33. Hormones TE, Group BCC. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 2010; 11 (6): 530–42.
34. Huang YF et al. Circulating IGF system and treatment outcome in epithelial ovarian cancer. Endocrine-related cancer 2014; 21 (2): 217–29.
35. Ioannou N et al. Treatment with a combination of the ErbB (HER) family blocker afatinib and the IGF-IR inhibitor, NVP-AEW541 induces synergistic growth inhibition of human pancreatic cancer cells. BMC cancer 2013; 13 (1): 41.
36. Kauppinen‐Mäkelin R et al. Increased cancer incidence in acromegaly–a nationwide survey. Clin Endocrinol 2010; 72 (2): 278–9.
37. Khromova N et al. Downregulation of VEGF-C expression in lung and colon cancer cells decelerates tumor growth and inhibits metastasis via multiple mechanisms. Oncogene 2011; 31 (11): 1389–97.
38. Liang B et al. Elevated VEGF concentrations in ascites and serum predict adverse prognosis in ovarian cancer. Scan J Clin Lab Investiga 2013; 73 (4): 309–14.
39. Lu L et al. The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer. Clin Cancer Res 2006; 12 (4): 1208–14.
40. Ludovini V et al. Concomitant high gene copy number and protein overexpression of IGF1R and EGFR negatively affect disease-free survival of surgically resected non-small-cell-lung cancer patients. Cancer Chemother Pharmacol 2013; 71 (3): 671–80.
41. Mikami K et al. Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A nested case-control study in large scale cohort study in Japan. Asian Pacific J Cancer Prevent: APJCP 2009; 10: 57–61.
42. Molife LR et al. The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study. Br J Cancer 2010; 103 (3): 332–9.
43. Moroney JW, Sood AK, Coleman RL. Aflibercept in epithelial ovarian carcinoma. Future Oncology 2009; 5 (5): 591–600.
44. Nakazawa Y et al. A multi‐targeting strategy using lenvatinib and golvatinib: Maximizing its anti‐angiogenesis activity in preclinical cancer model. Cancer Sci 2014.
45. National cancer institute. Surveillance, epidemiology, and end results program. http://seer.cancer.gov/statfacts/html/ovary.html
46. Park JH et al. Matrix metalloproteinase 9 promotes breast cancer through regulation of insulin-like growth factor-binding proteins. Cancer Res 2012; 72 (8 Suppl.): 2465.
47. Pengchong H, Tao H. Expression of IGF-1R, VEGF-C and D2-40 and their correlation with lymph node metastasis in endometrial adenocarcinoma. Eur J Gynaecol Oncol 2010; 32 (6): 660–4.
48. Reinhardt HC, Schumacher B. The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends in Genetics 2012; 28 (3): 128–36.
49. Rinaldi S et al. Serum levels of IGF‐I, IGFBP‐3 and colorectal cancer risk: results from the EPIC cohort, plus a meta‐analysis of prospective studies. Int J Cancer 2010; 126 (7): 1702–15.
50. Salvesen HB, Haldorsen IS, Trovik J. Markers for individualised therapy in endometrial carcinoma. Lancet Oncol 2012; 13 (8): e353–e361.
51. Samani AA et al. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocrine Rev 2007; 28 (1): 20–47.
52. Sayer RA et al. High insulin-like growth factor-2 (IGF-2) gene expression is an independent predictor of poor survival for patients with advanced stage serous epithelial ovarian cancer. Gynecol Oncol 2005; 96 (2): 355–61.
53. Soufla G, Sifakis S, Spandidos DA. FGF2 transcript levels are positively correlated with EGF and IGF-1 in the malignant endometrium. Cancer letters 2008; 259 (2): 146–55.
54. Spentzos D et al. IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer. Endocrine-related Cancer 2007; 14 (3): 781–90.
55. Steuerman R, Shevah O, Laron Z. Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies. Eur J Endocrinol 2011; 164 (4): 485–9.
56. Tas F et al. Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) in patients with epithelial ovarian cancer. Tumor Biol 2014; 35 (4): 3125–32.
57. Wagner AD et al. Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer. Cochrane Database Syst Rev 2012; 7.
58. Wang F et al. Vascular endothelial growth factor-regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases. Int J Cancer 2006; 118 (4): 879–88.
59. Wang H et al. The expression of VEGF and Dll4/Notch pathway molecules in ovarian cancer. Clinica Chimica Acta 2014; 436: 243–48.
60. Werner H, Bruchim I. IGF-1 and BRCA1 signalling pathways in familial cancer. Lancet Oncol 2012; 13 (12): e537–e544.
61. Wong C, Wellman TL, Lounsbury KM. VEGF and HIF-1a expression are increased in advanced stages of epithelial ovarian cancer. Gynecol Oncol 2003; 91 (3): 513–7.
2. Каприн А.Д., Старинский В.В., Петрова Г.В. Злокачественные новообразования в России в 2013 году (заболеваемость и смертность). М.: МНИОИ им. П.А.Герцена, 2015. / Kaprin A.D., Starinskii V.V., Petrova G.V. Zlokachestvennye novoobrazovaniia v Rossii v 2013 godu (zabolevaemost' i smertnost'). M.: MNIOI im. P.A.Gertsena, 2015. [in Russian]
3. Клиническая онкогинекология: Руководство для врачей. Под ред. В.П.Козаченко. М.: Медицина, 2005. / Klinicheskaia onkoginekologiia: Rukovodstvo dlia vrachei. Pod red. V.P.Kozachenko. M.: Meditsina, 2005. [in Russian]
4. Хохлова С.В. Роль бевацизумаба в лечении рака яичников. Онкогинекология. 2012; 3: 33–45. / Khokhlova S.V. Rol' bevatsizumaba v lechenii raka iaichnikov. Onkoginekologiia. 2012; 3: 33–45. [in Russian]
5. Чиссов В.И., Старинский В.В., Петрова Г.В.. Злокачественные новообразования в России в 2011 году (заболеваемость и смертность). М.: МНИОИ им. П.А.Герцена, 2013. / Chissov V.I., Starinskii V.V., Petrova G.V.. Zlokachestvennye novoobrazovaniia v Rossii v 2011 godu (zabolevaemost' i smertnost'). M.: MNIOI im. P.A.Gertsena, 2013. [in Russian]
6. An Y et al. Local expression of insulin-like growth factor-I, insulin-like growth factor-I receptor, and estrogen receptor alpha in ovarian cancer. Oncol Res Treat 2009; 32 (11): 638–44.
7. Bao B et al. Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment. PloS one 2012; 7 (12): e50165.
8. Baxter RC. IGF binding proteins in cancer: mechanistic and clinical insights. Nature Rev Cancer 2014; 14 (5): 329–41.
9. Belfiore A, Malaguarnera R. Insulin receptor and cancer. Endocrine-related cancer 2011; 18 (4): R125–R147.
10. Beltran PJ et al. Ganitumab (AMG 479) Inhibits IGF-II–Dependent Ovarian Cancer Growth and Potentiates Platinum-Based Chemotherapy. Clin Cancer Res 2014; 20 (11): 2947–58.
11. Brokaw J et al. IGF-I in epithelial ovarian cancer and its role in disease progression. Growth Factors 2007; 25 (5): 346–54.
12. Bruchim I et al. BRCA1/2 germline mutations in Jewish patients with uterine serous carcinoma. Int J Gynecol Cancer 2010; 20; 7: 1148–53.
13. Bruchim I, Sarfstein R, Werner H. The IGF hormonal network in endometrial cancer: functions, regulation, and targeting approaches. Frontiers in Endocrinol 2014; 5.
14. Brustmann H. Vascular endothelial growth factor expression in serous ovarian carcinoma: relationship with topoisomerase IIa and prognosis. Gynecol Oncol 2004; 95 (1): 16–22.
15. Burger RA et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011; 365 (26): 2473–83.
16. Cao Y et al. Prediagnostic plasma IGFBP‐1, IGF‐1 and risk of prostate cancer. Int J Cancer 2015; 136 (10): 2418–26.
17. Chakraborty AK, Welsh A, DiGiovanna MP. Co-targeting the insulin-like growth factor I receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer cell lines. Breast Cancer Res Treat 2010; 120 (20): 327–35.
18. Chen H et al. Correlation of the expressions of VEGF-C and VEGFR-3 to the pathological grade of prostate cancer. Nan fang yi ke da xue xue bao. J South Med Univ 2011; 31 (1): 155–9.
19. Cheng D, Liang B, Li Y. Serum vascular endothelial growth factor (VEGF-C) as a diagnostic and prognostic marker in patients with ovarian cancer. PloS One 2013; 8 (2): e55309.
20. Crociani O et al. hERG1 channels regulate VEGF-A secretion in human gastric cancer: clinicopathological correlations and therapeutical implications. Clin Cancer Res 2014; 20 (6): 1502–12.
21. Evans T et al. Phase I dose-escalation study of continuous oral dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR), in patients with advanced solid tumors. ASCO Meeting Abstracts 2010; 28: 2531.
22. Flannery CA et al. SAT-0017: Differential Expression of IR-a, IR-B and IGF-1R in Endometrium Reflects Physiology during the Menstrual Cycle and Demonstrates a Distinct Expression Signature in Endometrial Adenocarcinoma. 2014.
23. Gadducci A et al. Vascular endothelial growth factor (VEGF) expression in primary tumors and peritoneal metastases from patients with advanced ovarian carcinoma. Anticancer Res 2002; 23 (3C): 3001–8.
24. Gao J et al. Targeting the insulin-like growth factor axis for the development of novel therapeutics in oncology. Cancer Res 2012; 72 (10): 3–12.
25. Garcı́a-Echeverrı́a C et al. In vivo antitumor activity of NVP-AEW541—a novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell 2004; 5 (3): 231–9.
26. Gotlieb WH et al. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol 2012; 13 (20): 154–62.
27. Guleria S, Sharma J, Kaushik S. Laron syndrome. J Postgraduate Med 2014; 60 (3): 322.
28. Gungor A et al. FRI-319: Hypoinsulinemic Hypoglycemia Secondary to Solitary Fibrous Tumor of the Pleura: Doege-Potter Syndrome; A Case Report 2015.
29. Haluska P et al. Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Clin Cancer Res 2014; 20 (18): 4747–57.
30. Harb WA et al. Final results of a phase I study evaluating the combination of linsitinib, a dual inhibitor of insulin-like growth factor-1 receptor (IGF-1R), and insulin receptor (IR) with weekly paclitaxel (PAC) in patients (Pts) with advanced solid tumors. J Clin Oncol 2013; 31 (15).
31. He L, He J, Zhao X. Expression of VEGF‐D in epithelial ovarian cancer and its relationship to lymphatic metastasis. Asia‐Pacific J Clin Oncol 2013.
32. Herr D et al. VEGF induces ascites in ovarian cancer patients via increasing peritoneal permeability by downregulation of Claudin 5. Gynecol Oncol 2012; 127 (1): 210–6.
33. Hormones TE, Group BCC. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 2010; 11 (6): 530–42.
34. Huang YF et al. Circulating IGF system and treatment outcome in epithelial ovarian cancer. Endocrine-related cancer 2014; 21 (2): 217–29.
35. Ioannou N et al. Treatment with a combination of the ErbB (HER) family blocker afatinib and the IGF-IR inhibitor, NVP-AEW541 induces synergistic growth inhibition of human pancreatic cancer cells. BMC cancer 2013; 13 (1): 41.
36. Kauppinen‐Mäkelin R et al. Increased cancer incidence in acromegaly–a nationwide survey. Clin Endocrinol 2010; 72 (2): 278–9.
37. Khromova N et al. Downregulation of VEGF-C expression in lung and colon cancer cells decelerates tumor growth and inhibits metastasis via multiple mechanisms. Oncogene 2011; 31 (11): 1389–97.
38. Liang B et al. Elevated VEGF concentrations in ascites and serum predict adverse prognosis in ovarian cancer. Scan J Clin Lab Investiga 2013; 73 (4): 309–14.
39. Lu L et al. The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer. Clin Cancer Res 2006; 12 (4): 1208–14.
40. Ludovini V et al. Concomitant high gene copy number and protein overexpression of IGF1R and EGFR negatively affect disease-free survival of surgically resected non-small-cell-lung cancer patients. Cancer Chemother Pharmacol 2013; 71 (3): 671–80.
41. Mikami K et al. Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A nested case-control study in large scale cohort study in Japan. Asian Pacific J Cancer Prevent: APJCP 2009; 10: 57–61.
42. Molife LR et al. The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study. Br J Cancer 2010; 103 (3): 332–9.
43. Moroney JW, Sood AK, Coleman RL. Aflibercept in epithelial ovarian carcinoma. Future Oncology 2009; 5 (5): 591–600.
44. Nakazawa Y et al. A multi‐targeting strategy using lenvatinib and golvatinib: Maximizing its anti‐angiogenesis activity in preclinical cancer model. Cancer Sci 2014.
45. National cancer institute. Surveillance, epidemiology, and end results program. http://seer.cancer.gov/statfacts/html/ovary.html
46. Park JH et al. Matrix metalloproteinase 9 promotes breast cancer through regulation of insulin-like growth factor-binding proteins. Cancer Res 2012; 72 (8 Suppl.): 2465.
47. Pengchong H, Tao H. Expression of IGF-1R, VEGF-C and D2-40 and their correlation with lymph node metastasis in endometrial adenocarcinoma. Eur J Gynaecol Oncol 2010; 32 (6): 660–4.
48. Reinhardt HC, Schumacher B. The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends in Genetics 2012; 28 (3): 128–36.
49. Rinaldi S et al. Serum levels of IGF‐I, IGFBP‐3 and colorectal cancer risk: results from the EPIC cohort, plus a meta‐analysis of prospective studies. Int J Cancer 2010; 126 (7): 1702–15.
50. Salvesen HB, Haldorsen IS, Trovik J. Markers for individualised therapy in endometrial carcinoma. Lancet Oncol 2012; 13 (8): e353–e361.
51. Samani AA et al. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocrine Rev 2007; 28 (1): 20–47.
52. Sayer RA et al. High insulin-like growth factor-2 (IGF-2) gene expression is an independent predictor of poor survival for patients with advanced stage serous epithelial ovarian cancer. Gynecol Oncol 2005; 96 (2): 355–61.
53. Soufla G, Sifakis S, Spandidos DA. FGF2 transcript levels are positively correlated with EGF and IGF-1 in the malignant endometrium. Cancer letters 2008; 259 (2): 146–55.
54. Spentzos D et al. IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer. Endocrine-related Cancer 2007; 14 (3): 781–90.
55. Steuerman R, Shevah O, Laron Z. Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies. Eur J Endocrinol 2011; 164 (4): 485–9.
56. Tas F et al. Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) in patients with epithelial ovarian cancer. Tumor Biol 2014; 35 (4): 3125–32.
57. Wagner AD et al. Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer. Cochrane Database Syst Rev 2012; 7.
58. Wang F et al. Vascular endothelial growth factor-regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases. Int J Cancer 2006; 118 (4): 879–88.
59. Wang H et al. The expression of VEGF and Dll4/Notch pathway molecules in ovarian cancer. Clinica Chimica Acta 2014; 436: 243–48.
60. Werner H, Bruchim I. IGF-1 and BRCA1 signalling pathways in familial cancer. Lancet Oncol 2012; 13 (12): e537–e544.
61. Wong C, Wellman TL, Lounsbury KM. VEGF and HIF-1a expression are increased in advanced stages of epithelial ovarian cancer. Gynecol Oncol 2003; 91 (3): 513–7.
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1. Davydov M.I., Aksel' E.M. Statistika zlokachestvennykh novoobrazovanii v Rossii i stranakh SNG v 2012 g. M.: RONTs im. N.N.Blokhina, 2014; s. 51–66. [in Russian]
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Авторы
Р.И.Князев*1, И.В.Поддубная1, В.В.Баринов2, И.И.Бокин1
1 ГБОУ ДПО Российская медицинская академия последипломного образования Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1;
2 ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*sluwba@mail.ru
1 ГБОУ ДПО Российская медицинская академия последипломного образования Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1;
2 ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*sluwba@mail.ru
________________________________________________
R.I.Knyazev*1, I.V.Poddubnaya1, V.V.Barinov2, I.I.Bokin1
1 Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian. 125993, Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1;
2 N.N.Blokhin Russian Cancer Research Center. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*sluwba@mail.ru
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